P1451: PUBERTAL DEVELOPMENT OF TRANSFUSION DEPENDENT THALASSEMIA PATIENTS AT THE ERA OF ORAL CHELATION WITH DEFERASIROX: RESULTS OF THE FRENCH NATIONAL REGISTRY NATHALY
Authors: Mathilde Veneziano, Audrey Benoit, Yoann Huguenin, Anne Lambilliotte, Marie-Pierre Castex, Stephanie Gourdon, Ghislaine Ithier, Kamila Kebaili, Pierre-Simon Rohrlich, Corinne Pondarre, Abdourahim Chamouine, Pauline Simon, Placide Agbo-Kpati-Kokou, Slimane Allali, Sandrine Baron-Joly, Sophie Bayart, Nicolas Billaud, Valentine Brousse, Cecile Dumesnil, Nathalie Garnier, Isabelle Guichard, Laure Joseph, Annie Kamdem, Julie Maitre, Catherine Mathey, Catherine Paillard, Aurélie Phulpin, Cécile Renard, Cecile Stoven, Mohamed Touati, Capucine Trochu, Suzanne Mathieu, Julia Vergier, Catherine Badens, Szepetowski Sarah, Isabelle Thuret
Journal: HemaSphere (2023)

Topic: 27. Thalassemias Background: Endocrinopathies remain the main complication of iron overload in Transfusion Dependent Thalassemia (TDT), hypogonadism, generally due to oxidative stress related pituitary damage, being the most frequent and often the earliest manifestation. A well-managed chelation therapy initiated during infancy reduces the risk of pubertal delay and hypogonadism. Few data about the current pubertal development of TDT patients receiving DFX are available in literature. Aims: The aim of this national study was to evaluate pubertal development and hypogonadism in TDT adolescents and young adults included in the French National Thalassemia Registry (NaThalY) who received oral chelation with DFX. Methods: This retrospective study concerned all TDT patients included in the national registry (HSCT recipients excluded) who received DFX for at least three years before puberty. Patients were born between 1997 (maximum age of 10 years when DFX was marketed in 2007) and 2009 (evaluable for puberty in 2022). Delayed puberty was defined as lack of testicular development at 14 years old in boys and absence of thelarche at 13 years old in girls. Simple delayed puberty was defined as puberty with a delayed onset but then proceeding normally without the need for any treatment to achieve full pubertal development and hypogonadism as insufficient synthesis of sexual hormones. Results: Fifty patients fulfilled inclusion criteria. Their median age at evaluation was 18 years (range 13-24) and 25 patients (50%) were male. The median duration of DFX chelation before puberty was 7 years (3 -12). 80% of patients were born in France. Regular transfusion regimen and chelation therapy were initiated early, at 1.3 years (0.2-4) and 3 years (1-6) respectively. The median age at puberty onset was 14 years in males and 12 years in females with a median age at first menstruation of 13.5 years (Table). Ten patients (20%) had pubertal development anomalies or hypogonadism. Six patients had simple pubertal delay (n=5) or a transient arrest of puberty with a spontaneous favorable outcome (n=1). One patient developed persistent primary amenorrhea despite a one-year estrogen-progestogen hormone therapy and three others had early secondary amenorrhea: one had a severe chronic iron overload, the second received hormone replacement therapy for a central and peripheral hypogonadism with premature ovarian insufficiency and the third patient had secondary amenorrhea just after a normal pregnancy (the only pregnancy registered in the cohort) currently under investigation. These 10 patients (median age of 20.5 years, range 16-24) had all a beta0/0 genotype and 7/10 experienced a history of severe iron overload (Serum ferritin > 2500 ug/L or liver iron concentration > 15 mg/g). Nonetheless the duration of DFX before puberty and the age at the start of chelation were similar to the other 40 patients with no delay in puberty onset. The final height reached in 35 patients was slightly reduced (-0.7 DS) with a median pubertal growth spurt (difference between final height and prepubertal height) of 18 cm in girls and 21.5 cm in boys. Summary/Conclusion: In adolescents and young adults starting chelation therapy early and receiving before puberty a median of 7 years of DFX, the residual frequency of pubertal anomalies or hypogonadism was of 20% half of them presenting a simple pubertal delay. A pubertal growth spurt was observed leading to a final height only mildly reduced. Specialized follow-up of puberty even in the absence of abnormality is mandatory in TDT children. In the next years the frequency of hypogonadism in young adults could be also assessed.Keywords: Iron overload, Blood transfusion, Iron chelation, beta thalassemia